The number of patients who needed to treat to prevent one breast cancer with exemestane therapy was 94 in three years. That number was projected to drop to 26 in five years, the group reported here at the American Society of Clinical Oncology meeting and simultaneously online in the New England Journal of Medicine.

By comparison, five years of tamoxifen reduces breast cancer incidence by about 50% in high-risk women, while the same strategy with sister drug raloxifene (Evista) cuts risk by 38%.

Although both of those drugs are approved by the FDA for reducing breast cancer risk, uptake for this purpose has been "vanishingly rare," noted Nancy E. Davidson, MD, of the University of Pittsburgh Cancer Institute, and Thomas W. Kensler, PhD, of the UPMC Cancer Centers in Pittsburgh, in an accompanying NEJM editorial.

There's no reason for that trend to continue because there are now at least three proven tools in the armamentarium, and the knowledge to use them, the editorialists argued.

"We have run out of excuses," they wrote. "What are we waiting for?"

The researchers suggested that exemestane's lower profile of side effects may make it more acceptable.

In the study, the aromatase inhibitor did not carry a higher risk of skeletal fractures, cardiovascular events, other cancers, or treatment-related deaths, and had a "minimal" comparative effect on quality-of-life.

Exemestane was associated with a higher rate of adverse events, though most women in both groups reported them (88% versus 85% with placebo, P=0.003).

The researchers characterized these women as moderate risk, but the editorialists called it a high-risk cohort.

The final analysis was triggered by diagnosis of just 43 invasive breast cancer, resulting in "admittedly short" follow up and few overall events, the editorialist noted.

Yet exemestane also reduced risk of precursor lesions, such as DCIS, "suggesting possible further reductions in invasive cancers during long-term follow-up," Goss and colleagues pointed out in the study.

However, not all of the experts were convinced that exemestane will really shift the balance toward chemoprevention without mortality data.

"Because [tamoxifen and raloxifene] decrease the risk for developing breast cancer, but do not clearly decrease the risk of death, most patients opt not to take them," wrote Joanne Mortimer, MD, director of the Women's Cancers Program at City of Hope Comprehensive Cancer Center in Duarte, Calif., in an email to MedPage Today.

Another concern that may limit exemestane in this setting is that, despite the lower risk of serious adverse events in terms of thromboembolic events and uterine cancer, women generally do not feel as well on aromatase inhibitors as they do when taking tamoxifen, noted Kent Osborne, MD, director of the breast center at Baylor College of Medicine in Houston.

"They do have joint stiffness, vaginal dryness, and bone loss that affect a woman's quality of life," he wrote in an email to ABC News and MedPage Today. "These side effects are much less on tamoxifen, and tamoxifen has favorable affects on bone and cholesterol."

Other leading oncologists contacted by ABC News in collaboration with MedPage Today pointed out that tamoxifen has data showing chemoprevention in pre-menopausal women, whereas exemestane would only be an option for post-menopausal women.

Jennifer Litton, MD, of the MD Anderson Cancer Center in Houston, suggested that the MAP.3 results could be practice changing by providing post-menopausal women another option.

But she also called for longer follow up to determine whether exemestane has the same durable effects as tamoxifen beyond five years of treatment.

This article was developed in collaboration with ABC News.

The study was funded by the Canadian Cancer Society Research Institute, Pfizer, the Canadian Institutes for Health Research, and the Avon Foundation.

Goss reported board membership with Pfizer/Wyeth.

Davidson, Kensler, and Mortimer reported having no conflicts of interest to disclose.

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